Infusion site for improved mixing of fluids

ABSTRACT

The invention relates to a blood line ( 108 ) comprising an infusion site ( 145 ) intended to inject into the line a solution comprising: —a first main channel ( 200 ) having a first passage section, —a second main channel ( 220 ) having a second passage section, —means for the formation ( 210 ) of a turbulence area located downstream from the first main channel, located upstream from the second main channel, these formation means comprising a first fluid passage means ( 224 ) defining a reduction ( 225 ) in the passage section and whose smallest passage section is smaller than the first passage section and smaller than the second fluid passage section, —a secondary channel ( 230 ) comprising an inlet ( 231 ) for letting in the solution and an outlet ( 232 ) in fluid communication with the first main channel or the means for the formation of a turbulence area or the second main channel.

BACKGROUND Technical Field of the Invention

The object of the present invention is a blood treatment device by wayof extracorporeal circulation with anticoagulant pre-infusion, adisposable line to be used in an extracorporeal circuit for bloodcirculation with anticoagulant pre-infusion and a method foranticoagulation of blood treated by way of extracorporeal circulation.

Prior Art

Extracorporeal blood treatment is used for patients who are not able toeffectively eliminate substances from blood, e.g. for a patientsuffering from a temporary or permanent renal insufficiency. Thesepatients and others can undergo a extracorporeal blood treatment so asto add or eliminate substances to or from blood, to keep an acid-basebalance or to remove excess corporeal fluids for instance.Extracorporeal blood treatment is typically used for withdrawingundesired substances or molecules from a patient's blood and/or foradding beneficial substances or molecules to blood.

Extracorporeal blood treatment is typically carried out by withdrawingblood from the patient continuously, introducing blood into a maincompartment of a filter, in which blood gets through a semipermeablemembrane (see FIG. 3). The semipermeable membrane lets undesiredsubstances contained in blood through in a selective manner, from themain to the secondary compartment, and also lets beneficial substancescontained in the liquid in the secondary compartment through in aselective way, to blood getting through the main compartment, dependingon the type of treatment.

A number of extracorporeal blood treatments can be carried out with thesame machine. In an ultrafiltration treatment (UF), the undesiredsubstances are removed from blood by convection through the membrane inthe secondary compartment.

In a hemofiltration treatment (HF), blood flows through thesemipermeable membrane as in UF, and beneficial substances are added toblood, typically by introducing a fluid into blood, both before andafter it gets through the filter and before it is returned to thepatient.

In a hemodialysis treatment (HD), a secondary fluid containingbeneficial substances is introduced into the secondary compartment ofthe filter. The undesired substances contained in blood get through thesemipermeable membrane and into the secondary fluid, and the beneficialsubstances can get from the secondary fluid through the membrane intoblood.

In a hemodiafiltration treatment (HDF), blood and the secondary fluidexchange their substances as for HD, and moreover substances are addedto blood, typically introducing a fluid into treated blood before thelatter is returned to the patient as for HF.

For carrying out a hemodialysis, hemofiltration or hemodiafiltrationsession, blood circulating in the extracorporeal circulation line has toundergo an anticoagulation treatment so as to prevent blood contactingsynthetic material (circulation lines, fibers of the dialyzer) fromcoagulating. Most often, this anticoagulation occurs with heparin, whichis known for its anticoagulant properties. Heparin is injected inpre-infusion into the arterial line of the device and is thus present inthe whole extracorporeal blood circuit, •from pre-infusion up to bloodreturn into the patient. As a consequence, heparin doses areadministered to the patient through the blood return line. Even ifcoagulation should be prevented in the extracorporeal circulation line,in some cases the risk of bleeding for the patient can represent adanger. It is especially the case of highly hemorrhagic patients (e.g.in the days following a major surgical operation) or also of patientsthat are hypersensitive to heparin. The anticoagulation treatment withheparin can therefore prove to be dangerous for the patient due toheparin injection through the blood return line to the patient.

FIG. 1 shows a blood treatment device by way of extracorporealcirculation 1 at the state of the art, comprising a filter 2 having afirst compartment 3 and a second compartment 4 separated by asemipermeable membrane 5. The device includes •an arterial line 6connected to the first compartment 3 of the filter for circulating bloodtaken from a patient 7, and a venous line 8 getting out of the firstcompartment of the filter. A pre-infusion channel 9 is connected to acontainer 10 containing a heparin solution and is attached to thearterial line 6, the solution having the purpose of preventing bloodfrom coagulating outside the patient's body, a drain channel 11 gettingout of the second compartment 4 of the filter. An air separator 12 isattached to the venous line 8. The air separator 12 includes also an airdetector 13, and a clamp 14 is placed on the venous line 8 downstreamfrom the air separator 12, i.e. downstream in the sense of bloodcirculation in the venous line 8. The clamp enables to stop blood flowif air bubbles are detected by the detector 13 before blood is returnedto the patient 7.

The heparin solution, as mentioned above, acts against blood coagulationboth in the whole device 1 and in the patient's body. Therefore, heparinreturn and injection into the patient's body 7, can prove to bedangerous.

Patent application PCT/EP00/03583, whose hydraulic circuit is shown inFIG. 2, relates to an substitution infusion fluid, especially for use inblood hemofiltration, and to a citrate anticoagulant solution for localanticoagulation. In order to prevent blood coagulation, during ahemodialysis session, it is known that citrate ions can be used asanticoagulant.

Citrate ions, added to blood in the extracorporeal circuit beforegetting into the artificial kidney, act as anticoagulants thanks totheir ability of chelating calcium ions. During hemofiltration, a partof citrate ions (mainly those chelated with blood calcium) gets throughthe artificial kidney. This appreciable calcium loss is compensated by apost-filter or systemic calcium infusion. Citrate ions act asanticoagulants only in the extracorporeal circuit, since when they getinto the patient's systemic circulation, they are rapidly metabolizedinto bicarbonate ions. The risk of bleeding complications due tosystemic anticoagulation is avoided. In FIG. 2, the device 1 comprises afilter 2 having a first compartment 3 and a second compartment 4separated by a semipermeable membrane 5. The device includes an arterialline 6 connected to the first compartment 3 of the filter forcirculating blood taken from a patient 7, and a venous line 8 gettingout of the first compartment of the filter. A pre-infusion channel 9containing an anticoagulant, trisodium citrate, is connected to acontainer 10 including a solution of citrate ions attached to thearterial line 6, the solution having the purpose of preventing bloodfrom coagulating outside the patient's body. A drain channel 11 isattached at the outlet of the second compartment 4 of the filter and anair separator 12 is attached to the venous line 8. The venous line 8includes, beyond the bubble trap 12, a channel 13 connected to acontainer 14 containing a solution reestablishing blood ion balance. Asa matter of fact, the citrate solution makes blood anticoagulable bydecalcifying it upstream from the filter. This channel 13 is attacheddownstream from the bubble trap 12, i.e. downstream in the sense ofblood circulation in the venous line 8 before blood is returned to thepatient 7.

As a matter of fact, in order to reestablish a correct hemostasis, bloodion balance has to be reestablished—especially by recalcifying it—at theoutlet of the filter.

It is known to carry out this infusion of solution reestablishing ionbalance also by injecting calcium into a bubble trap present on thevenous line.

As an alternative, it is eventually known to carry out this infusion ofsolution reestablishing blood balance directly in a patient's vascularaccess separated from the extracorporeal circuit (not shown). Withrespect to the first technique, the drawback of this second techniqueconsists in the need for an independent control of the pump or syringeadministering citrate by infusion and of the pump administering thesolution reestablishing ion balance by infusion.

We shall refer to the technique consisting in infusing thereestablishing solution into the blood extracorporeal circuit. Thistechnique makes use of a bubble trap present on the venous line or asimple infusion site present on the venous line.

Such an infusion site is generally made up of a main channel having thesame diameter as the blood line, and of a secondary channel having asmaller diameter, attached perpendicularly on the main channel on oneside and comprising a secondary inlet site for the infusion liquid. Thissecondary inlet site can be an “empty” channel where the liquid getsthrough or a channel provided in its section with a membrane apt to bepierced by the needle of a syringe containing the solution to beinfused.

The Applicant has made in-vitro and in-vivo tests on sheep models forextracorporeal circulation with a citrate anticoagulation on thearterial line (in pre-infusion) and a calcium injection on the venousblood line (in post-infusion). First tests have been carried out byinfusion of ion reestablishing solution directly into the bubble trap ofthe venous line of the extracorporeal circuit, and other tests have beencarried out with a traditional infusion device located on the venousline.

A recurrent problem related to the mixing of the reestablishing solutionwith dialyzed blood has been observed: this mixing does not occuruniformly and there are significant local coagulation problems, whichbecome evident especially with the appearance of coagulation filaments.

Therefore, there was the need to provide a solution so that the infusionof reestablishing solution has a significantly reduced coagulation. Tothis purpose, the inventors have thought to optimize the mixing ofdialyzed blood of the venous line and calcium injected into the venousline

Disclosure of the Invention

The goal of the present invention is to solve this problem concerningcoagulation in the blood extracorporeal circuit due to the infusion ofthe solution reestablishing ion balance.

To this purpose, the invention related to a blood line (108) forextracorporeal blood or plasma. treatment comprising:

-   -   a first line portion (134) intended to be connected to the        outlet of a filter,    -   a second line portion (137) intended to be connected to a        patient's vascular access,    -   an infusion site (145) acting between the first line portion        (134) and the second line portion (137), and intended to inject        into the blood line a solution reestablishing blood or plasma        ion balance, comprising:    -   a first main channel (200) in fluid communication with the first        line portion (134) and having a first passage section,    -   a second main channel (220) in fluid communication with the        second line portion (137) and having a second passage section,    -   means for the formation (210) of a turbulence area located        downstream from and in fluid communication with the first main        channel, located upstream from and in fluid communication with        the second main channel, these formation means comprising a        first fluid passage means (224) defining a reduction (225) in        the passage section and whose smallest passage section is        smaller than the first passage section and smaller than the        second fluid passage section,    -   a secondary channel (230) comprising an inlet (231) for letting        in a solution reestablishing ion balance and an outlet (232) in        fluid communication with at least one of the three elements        chosen among the first main channel (200), the means for the        formation (210) of a turbulence area and the second main channel        (230).

The blood line is preferably used as venous line.

The invention also relates to a set of lines intended to be attached toa blood or plasma filter (102) comprising:

-   -   an arterial line (106) having a connector intended to be        connected to the first compartment (103) of a filter (102),    -   a pre-infusion channel (109) for a local anticoagulation        substance attached to the arterial line (106),    -   a blood line (108) according to the invention, wherein the inlet        (135) of the first line portion (134) is intended to be        connected to the outlet of the filter (102) and the outlet of        the second blood portion line (137) is intended to be connected        to a patient's vascular access.

The invention also relates to a blood or plasma treatment device by wayof extracorporeal circulation (101) comprising:

-   -   a filter (102) having a first (103) and a second (104)        compartment separated by a semipermeable membrane (105),    -   an arterial line (106) connected to the first compartment (103)        of the filter (102),    -   a pre-infusion channel (109) for a local anticoagulation        substance attached to the arterial line (106),

characterized in that it comprises a blood line (108) getting out of thefirst compartment (103) of the filter (102) according to the invention.

Eventually, the invention relates to a method for extracorporeal bloodtreatment carried out with the device according to the invention,including the following steps:

a) making blood or plasma flow through the arterial line (106),

b) infusing through the pre-infusion channel (109) a localanticoagulation substance in the arterial line (106),

c) filtering blood through the filter (102),

d) making filtered blood flow through the first portion of the bloodline (108),

e) making filtered blood flow in a reduction of the passage section ofthe infusion site, thus causing a turbulence in blood flow,

f) infusing through the secondary channel (230) of the infusion site(145) a solution for reestablishing ion balance,

g) making filtered blood mixed with the solution for reestablishing ionbalance flow through the second portion of the blood line (108),

wherein step f) is carried out straight before, during or straight afterstep e).

SHORT DESCRIPTION OF THE DRAWINGS

Further advantages and characteristics of the invention shall emergefrom the following description.

We shall make reference to the attached drawings, wherein:

FIG. 1 shows the state of the art concerning an apparatus forextracorporeal blood treatment with anticoagulation prevention by way ofheparin;

FIG. 2 shows the state of the art concerning an apparatus forextracorporeal blood treatment with anticoagulation prevention by way ofcitrate;

FIG. 3 shows the blood treatment device by way of extracorporealcirculation according to the invention;

FIG. 4 shows a disposable line for blood treatment by way ofextracorporeal circulation according to the invention;

FIGS. 5, 6 and 7 show in detail the injection site according to a firstembodiment of the invention, in sectioned front view, sectioned top viewand sectioned right view, respectively

FIG. 8 shows in detail the injection site according to a firstembodiment connected to a portion of the blood line, in exploded andsectioned front view;

FIGS. 9 and 10 show in detail the injection site according to a secondembodiment of the invention, in sectioned front view and sectioned leftview, respectively;

FIG. 11 shows in detail the injection site according to a secondembodiment connected to a portion of the blood line, in exploded andsectioned front view;

FIG. 12 shows in detail the injection site according to a thirdembodiment connected to a portion of the blood line, in exploded andsectioned front view;

FIGS. 13, 14, 15 and 16 show diagrams of embodiments of the infusionsite with constant section narrowing, their A-A section being in view;

FIGS. 17, 18, 19, 20, 21 and 22 show diagrams of embodiments of theinfusion site with partial separations, their A-A section being in view;

DETAILED DISCLOSURE OF EMBODIMENTS OF THE INVENTION

FIG. 3 shows the blood treatment device by way of extracorporealcirculation according to the invention, intended to carry out a dialysistreatment. The blood treatment device by way of extracorporealcirculation 101 according to the invention comprises a filter 102 havinga first 103 and a second compartment 104 separated by a semipermeablemembrane 105. Depending on the membrane, the filter (105) can be ahemofilter, a plasma filter, a dialyzer or a filter of other type. Asfar as the membrane is concerned, membranes used are hollow fibermembranes or plate or sheath membranes. An arterial line 106 isconnected to the first compartment 103 of the filter for circulatingblood taken from a patient 107. A blood line 108 is connected at theoutlet of the first compartment 103 of the filter. A pre-infusionchannel 109 for a local anticoagulation substance is attached to thearterial line 106. A drain channel 110 is connected at the outlet of thesecond compartment 104 of the filter. An air separator 111 is placed onthe blood line 108 and a post-infusion line 112 for a solution at leastpartially reestablishing blood ion balance is located downstream—i.e.downstream in the sense of blood circulation in the blood line 108—fromthe air separator 111. Eventually, an air detector 113 is locateddownstream from the post-infusion line 112.

It should be noted that FIG. 3 shows a treatment mode by way ofdialysis, though the invention applies to all types of extracorporealblood treatments mentioned above: hemofiltration, hemodiafiltration andso on, which can actually be implemented with a citrate anticoagulation.

FIG. 4 shows the disposable blood line 108 for use in a circuit for theextracorporeal circulation of blood having undergone a pre-infusion ofanticoagulant, comprising a first channel 134 with a first connection135 for attaching a filter, and a second connection 136. An airseparator 111 is attached to the second connection 136 downstream—i.e.downstream in the sense of blood circulation—from the first channel 134.The disposable blood line 108 also comprises a second channel 137 havinga third connection 138 for attaching the outlet of the air separator111, and a fourth connection 139 for attaching a patient's blood access.

The infusion site 145 is intended to receive a post-infusion line 112for a solution at least partially reestablishing blood ion balance andis in fluid communication with the second channel 137 and in fluidcommunication with the channel 134. The line further includes a firstportion 141 of the second channel 137 that is able to cooperate with theair detector 113 and placed downstream from the site 145. The firstportion 141 is optically coded, e.g. with different colors, with arelief, with a pipe having a different material, shape or size withrespect to the remaining line. The above described elements of the lineare not strictly necessary for implementing the invention, either.

FIG. 4 shows the infusion site 145 located between the bubble trap 111and the first portion 141 of the second channel 134. In this case, thesite is placed in the sense of blood circulation—upstream from the airdetector 113 and the air detector enables to monitor an undesired airintroduction, if any, into the circuit towards the patient.

However, as an alternative to the configuration of FIG. 4, the infusionsite can be located on the blood line downstream from the first portion141 that is able to cooperate with the air detector 113. In this case,the infusion line 112 is provided with a self-degassing filter enablingto place the connection of the line 112 as desired on the line 137,especially as close as possible to the connector 139, which makes thepresence of the detector 113 on the line 137 useless for the infusionline 112.

As shown on each of the FIGS. 8, 11 and 12, the invention is a bloodline (108) for extracorporeal blood or plasma treatment, comprising:

-   -   a first line portion (134) intended to be connected to the        outlet of a filter,    -   a second line portion (137) intended to be connected to a        patient's vascular access,    -   an infusion site (145) acting between the first line portion        (134) and the second line portion (137), and intended to inject        into the blood line a solution reestablishing blood or plasma        ion balance, comprising:    -   a first main channel (200) in fluid communication with the first        line portion (134) and having a first passage section,    -   a second main channel (220) in fluid communication with the        second line portion (137) and having a second passage section,    -   means for the formation (210) of a turbulence area located        downstream from and in fluid communication with the first main        channel, located upstream from and in fluid communication with        the second main channel, these formation means comprising a        first fluid passage means (224) defining a reduction (225) in        the passage section and whose smallest passage section is        smaller than the first passage section and smaller than the        second fluid passage section,    -   a secondary channel (230) comprising an inlet (231) for letting        in a solution reestablishing ion balance and an outlet (232) in        fluid communication with at least one of the three elements        chosen among the first main channel (200), the turbulence area        formation means (210) and the second main channel (230).

The assembly of the channels with the infusion site is not shown inFIGS. 8, 11 and 12 since the device is in an exploded view. Conversely,the device in FIG. 5 shows the finished device according to the assemblymode of the invention. The pipes are assembled by way of internalmounting. Assembly can be carried out by gluing mainly with a solvent orwith radiation (e.g. UV) polymerizing glue.

In order to optimize the mixing homogeneity of blood and calcium, thegeometry of the infusion site has been given the first place so as toenable the formation of a blood turbulence area integrated into theblood flow area. Indeed, it is important to increase the number ofReynolds so as to ensure the switch from a laminar flow to a turbulentflow in the injection site, which means homogenization of the twoliquids and prevents local coagulation due to an inaccurate mixing.

According to the invention, blood reaches this flow rate in the infusionsite and should be able to get out of it with the same flow rate perhour, and preferably substantially the same linear flow rate (ml/mm)after getting through the turbulence area (the smallest infusion flowrate as possible is added to the inlet flow rate).

A turbulence area is an area in which fluid flow becomes instable andperturbed, thus generating multiple whirlpools. The turbulent flow isopposed to the laminar flow. Reducing the passage section in theinfusion site enables to increase the number of Reynolds to a sufficientdegree so as to switch from a laminar to a turbulent flow, so as togenerate a turbulence, though leaving hemoglobin untouched and ensuringthe prescribed blood flow rate. As a matter of fact, it should be notedthat hemoglobin, more precisely red corpuscles, are not damaged duringtreatment, which enables to prevent a hemolysis that might be fatal tothe patient. Moreover, the blood flow rate should keep a given thresholdin order to prevent the treatment from getting longer.

Therefore, the solution enabling to reestablish ion balance (e.g.calcium) is injected directly close to the turbulence formation area.The turbulence formation area gets integrated into the disposable bloodline. Once more, turbulence intensity is optimized so as to ensure atthe same time a sufficient mixing and to prevent a significant hemolysisin the expected operating range.

The comparative tests on the infusion site according to the inventionshow highly positive results since the mix is homogenized withoutaltering any other treatment parameters. As a matter of fact, calciuminfusion close to the blood turbulence area inhibits the long threads offibrins observed on a prior art infusion site and no clots are observed,either. Tests have been carried out by periodically monitoringcoagulation time (APTT) and calcium, sodium and potassium as well as pH.

The turbulence area formation means (210) can comprise a secondary inlet(213), and the outlet (232) of the secondary channel of the site (230)is connected to said secondary inlet (213).

Alternatively, the first main channel (200) can include a secondaryinlet (shown schematically by arrow 3 in FIGS. 13 to 20), and the outlet(232) of the secondary channel of the site (230) is connected to saidsecondary inlet (arrow “3”). In this case, the outlet (232) of thesecondary channel of the site (230) is connected to said secondary inlet(213) straight downstream from the turbulence area formation means.

Still alternatively, the second main channel (220) includes a secondaryinlet (shown schematically by the arrows “1” and “1′” in FIGS. 13 to20), and the outlet (232) of the secondary channel of the site (230) isconnected to said secondary inlet (1, 1′). In this case, the outlet(232) of the secondary channel of the site (230) is connected to saidsecondary inlet (213) straight upstream from the turbulence areaformation means.

Continuous Section Narrowing:

Moreover, the first fluid passage means (224) of the turbulence areaformation means (210) can define a continuous section narrowing in thesense of fluid passage. More particularly, the first fluid passage means(224) of the turbulence area formation means (210) defined a constantnarrowing of internal circular section, thus resulting in an internalconical surface of revolution whose symmetry axis is the longitudinalaxis of the 10 first passage means. It has been shown that a constant,smooth, continuous and preferably progressive narrowing enables not tolimit hemolysis intensity. The number of Reynolds in the surface of thesmallest circular section (228) of the conical surface can be chosendepending of the expected operating range of the device. The number ofReynolds for a blood passage in the smallest circular section of theconical surface (228) can vary from about 500 to about 2,000.

Operating Range:

The number of Reynolds is chosen so as to obtain a compromise betweenhomogeneous mixing and hemolysis prevention as a function of the bloodflow rate range. The development of the number of Reynolds in section“g” for the two sizes of the components (calculation for a viscosity of3 cP) is shown in the following table:

Blood flow rate High flow version (FIGS. Low flow version ml/min. 5, 6and 7) (FIGS. 9 and 10) 50 442 75 663 100 590 880 150 880 1,330 20 1,1801,770 250 1,470 300 1,770 350 2,060

However, this table should not be deemed as limiting. The number ofReynolds can vary in the range [350, 3,000), preferably in the range[500, 2,000].

Furthermore, as is still shown in at least FIGS. 5 to 12, the turbulencearea formation means (210) can include a second fluid passage means(226) downstream from the first fluid passage means (224) defining anincrease (227) in the fluid passage section in the sense of fluidpassage. More particularly, the largest fluid passage section of thesecond fluid passage means (226) shall be smaller than said firstpassage section and smaller than said second passage section. Thus, theincrease (227) in the fluid passage section of the second fluid passagemeans (226) can define a shoulder perpendicular to the axis of thesecond fluid passage means (224).

Generally speaking, FIGS. 13 to 16 show turbulence area formation meanscomprising a constant narrowing of the blood passage section. The firstand second main channels of the site are shown with an arrow indicatingthe sense of blood passage. Three alternative preferred positions of theinlet of the secondary channel into the main channels of the site whichblood gets through are shown by numerals 1, 2 and 3. “1” corresponds toinjection straight downstream from the blood turbulence formation area;“2” corresponds to injection in the blood turbulence formation area, and“3” corresponds to injection straight upstream from the blood turbulenceformation area.

In FIG. 13 the turbulence area formation means comprise a constantnarrowing according to the longitudinal axis of the site, then a shortpipe portion with small diameter and, eventually, a shoulder enabling toget back to the starting diameter of the site and of the blood line.

FIG. 14 shows the same site as in FIG. 13 with a perpendicular elbowpipe.

FIG. 15 shows the same site as in FIG. 13 with a non-axial narrowing.

FIG. 16 shows the same site as in FIG. 13 with a square (and no longerround) passage section.

Each mode can be combined with another one for obtaining a furtherembodiment of the site.

Partial Separation(s):

Alternatively, the line according to the invention can have the firstfluid passage means (224) of the turbulence area formation means (220)comprising at least a partial separation (250) whose longitudinal planeis perpendicular to the longitudinal axis of the first passage means(224). This is shown in FIGS. 17 to 22. The mode comprising a partialseparation is shown in FIG. 17, when the partial separation concernedthe pipe wall, and alternatively in FIG. 20 when the partial separationis centered with respect to the tube.

The turbulence area formation means (220) can comprise at least twopartial separations (250) each longitudinal plane of which isperpendicular to the longitudinal axis of the first fluid passage means(224), divided according to a symmetry point located on saidlongitudinal axis. The mode including two partial separations is shownin FIG. 18 when the partial separations concern the pipe wall and, asshown in top view, the two separations substantially cover the whole ofthe pipe section. The mode including three partial separations is shownin FIG. 19 when the partial separations concern the pipe wall and, asshown in top view, the three separations substantially cover the wholeof the pipe section. When several partial separations are used, theseare distributed on the longitudinal axis of the pipe.

In FIGS. 17 to 22, three alternative position of the inlet of thesecondary channel in the main channels of the site which blood getsthrough are shown with numerals 1, 1′, 2, 2′ and 3. “1” corresponds toinjection straight downstream from the blood turbulence formation area;“1′”, “2” and “2′” correspond to injection in the blood turbulenceformation area, and “3” corresponds to injection straight upstream fromthe blood turbulence formation area.

More particularly, the secondary channel (230) for letting in the ionreestablishing solution in the site (145) can be integrated into one ofthe partial separations (250) and where the axis of the secondarychannel is perpendicular to the longitudinal axis of the first fluidpassage means (224). FIGS. 21 and 22 show this mode and differ in theoutlet in the calcium injection site, located at the end of the partialseparation transversally to blood sense (FIG. 21) or at the end of thepartial separation parallel to blood sense and downstream from thenarrowing.

It should be noted in general for all embodiments that injected calciumis not perturbed before its arrival in the main channel and that calciumis preferably let in by a pipe with a constant circular section,preferably with a smaller section than the one of the first and secondmain channels.

According to the invention, the turbulence area formation means (210)can be an elbow pipe or a straight pipe.

Moreover, the outlet of the secondary channel (230) of the infusion siteis connected to the secondary inlet of the turbulence area formationmeans (210), this secondary inlet (232) being located on the secondfluid passage means (224).

Distribution of Axes:

According to the invention:

-   -   the longitudinal axis of the secondary channel (230) of the site        for letting in a solution reestablishing ion balance can be        parallel to, preferably coaxial with the longitudinal axis of        the second main channel of the site,    -   the longitudinal axis of the secondary channel (230) of the site        can be perpendicular to the longitudinal axis of the second main        channel (220) of the site,    -   the longitudinal axis of the first main channel (200) of the        site can be perpendicular to the longitudinal axis of the second        main channel (220) of the site,    -   the longitudinal axis of the first channel (200) of the site can        be parallel to, preferably coaxial with the longitudinal axis of        the second main channel (220) of the site,    -   the respective axes of the first (210) and of the second (220)        main channel of the site and of the secondary channel (230) of        the site can be coplanar,    -   the longitudinal axis of the end of the first line portion (134)        connected to the site is coaxial with the longitudinal axis of        the first main channel (200) of the site,    -   the longitudinal axis of the end of the second line portion        (137) connected to the site is coaxial with the longitudinal        axis of the second main channel (200) of the site.

The above generally implies that the inlet and outlet of each channelare included in the axis.

Furthermore, the invention can comprise the following elements:

-   -   the secondary channel (230) of the infusion site is connected to        a bag or a syringe (133) containing liquid for reestablishing        ion balance,    -   the line comprises a bubble trap (111) acting on the first line        portion (134) preferably upstream (possibly downstream) from the        infusion site (145),    -   the infusion site (145) is made as one piece,    -   the infusion site (145) is made of rigid or semi-rigid        hemocompatible plastic material, preferably starting from        polyethylene terephthalate (PETG) or polytetrafluoroethylene        (PTFE-Teflon), Dacron (polyester), PVC.

Moreover, the set of lines according to the invention, as well as thedevice for blood treatment according to the invention, can furtherinclude:

-   -   a container for local anticoagulation substance connected to the        pre-infusion channel (109), and/or    -   a container for solution reestablishing ion balance 133 (e.g. a        bag, a syringe and so on) connected to the secondary channel        (230) of the infusion site.

All lines can be disposable, the blood device too.

The blood treatment device according to the invention can furthercomprise one and/or the other of the following elements:

-   -   a drain channel (110) getting out of the second compartment        (104) of the filter (102),    -   a container of local anticoagulation substance connected to the        pre-infusion channel (109),    -   a container of solution reestablishing ion balance (133)        connected to the secondary channel (230) of the infusion site,    -   an air detector (113) acting on the blood line downstream from        the infusion site (145),    -   an air separator (111) on the blood line (108), upstream from        the air detector.

By way of information, the infusion site shown in FIG. 3 has thefollowing sizes:

High flow version (e.g. Low flow version (e.g. FIGS. Side FIGS. 5, 6 and7) 9 and 10) a 6.55 4.75 b 4.15 2.87 c 3.18 3.18 d 0.80 0.80 e 9 9 f 6 6g 1.2 0.8

FIGS. 6 and 7 also contain sizes to an indicative purpose. All thesesizes are in no way limiting for the present description.

Advantages of the Invention

The invention has several advantages:

-   -   the device enables to homogenize blood and calcium injected,        thus preventing any formation of local coagulation (generally        observed as filament),    -   it requires no additional component normally used in the        extracorporeal blood circuit,    -   the reestablishing solution (calcium in particular) is mixed        with blood in a homogeneous manner and blood is not damaged by        the turbulence area,    -   the turbulence formation area is integrated into the disposable        blood line: this is no additional means or a means independent        from the extracorporeal circuit and it is not strictly necessary        to use a syringe.

1-34. (canceled)
 35. A method of anticoagulating blood treated duringextracorporeal circulation in an extracorporeal circulation blood orplasma treatment device, the extracorporeal circulation blood or plasmatreatment device comprising: a filter having a first compartment and asecond compartment separated by a semipermeable membrane; an arterialline in fluid communication with the first compartment of the filter; apre-infusion channel for a local anticoagulation substance in fluidcommunication with the arterial line; a container of a localanticoagulation substance in fluid communication with the pre-infusionchannel; a venous blood line in fluid communication with the firstcompartment of the filter, the venous blood line comprising: a firstline portion in fluid communication with an outlet of the filter, asecond line portion in fluid communication with a patient's vascularaccess, an infusion site between the first line portion and the secondline portion for injecting into the blood line a solution reestablishingblood or plasma ion balance, the infusion site comprising: a first mainchannel in fluid communication with the first line portion and having afirst passage section, a second main channel in fluid communication withthe second line portion and having a second passage section, and aturbulence area downstream from and in fluid communication with thefirst main channel, and upstream from and in fluid communication withthe second main channel, the turbulence area comprising a first fluidpassage defining a reduction in passage section having a smallestpassage section smaller than the first passage section and smaller thanthe second passage section, and a secondary channel comprising an inletfor the solution reestablishing blood or plasma ion balance and anoutlet in fluid communication with at least one of the first mainchannel, the turbulence area and the second main channel; and acontainer of solution reestablishing blood or plasma ion balance influid communication with the secondary channel of the infusion site viaa post-infusion line; the method comprising: a) flowing blood or plasmathrough the arterial line, b) infusing the local anticoagulationsubstance through the pre-infusion channel into the arterial line, c)filtering blood through the filter, d) flowing the filtered bloodthrough the first line portion of the venous blood line, e) flowing thefiltered blood in the turbulence area of the infusion site to cause aturbulence in blood flow, f) infusing the solution for reestablishingion balance through the secondary channel of the infusion site, and g)flowing the filtered blood mixed with the solution for reestablishingblood or plasma ion balance through the second portion of the bloodline, wherein step f) is carried out directly before, during or directlyafter step e).
 36. The method of claim 35, wherein the post-infusionline is internally mounted into the secondary channel, an outer surfaceof the post-infusion line portion being sealingly connected to an innersurface of a post-infusion passage section of the infusion site.
 37. Themethod of claim 35, wherein the first line portion is internally mountedinto the first main channel of the infusion site and the second lineportion is internally mounted into the second main channel of theinfusion site.
 38. The method of claim 35, wherein causing turbulence inblood flow includes switching from a laminar blood flow to a turbulentblood flow in the infusion site.
 39. The method of claim 38, furtherincluding increasing the Reynolds number to switch from the laminarblood flow to the turbulent blood flow.
 40. The method of claim 35,wherein causing turbulence in blood flow includes causing the blood flowto generate multiple whirlpools.
 41. The method of claim 35, wherein atleast one of the local anticoagulation substance includes citrate or thesolution reestablishing blood or plasma ion balance includes calcium.42. The method of claim 35, wherein the solution reestablishing blood orplasma ion balance is not perturbed before arrival in the at least oneof the first main channel, the turbulence area or the second mainchannel.
 43. The method of claim 35, comprising injecting the solutionreestablishing blood or plasma ion balance using a pipe having aconstant circular section, the constant circular section of the pipebeing smaller than any of the sections of the first main channel and thesecond main channel.
 44. The method of claim 35, wherein the turbulencearea includes a second fluid passage downstream from the first fluidpassage and defining an increase in fluid passage section, and whereinthe largest fluid passage section of the second fluid passage is smallerthan said first passage section and smaller than said second passagesection.
 45. The method of claim 44, wherein the increase in fluidpassage section of the second fluid passage defines a shoulderperpendicular to the longitudinal axis of the second fluid passage. 46.The method of claim 35, wherein the first fluid passage of theturbulence area defines a continuous section narrowing fluid passage.47. The method of claim 35, wherein the first fluid passage of theturbulence area has a constantly narrowing internal circular section,resulting in a conical internal surface having a symmetrical axis whichis the longitudinal axis of the first passage.
 48. The method of claim47, wherein the Reynolds number for blood flow in the smallest circularsection of the conical internal surface varies from 350 to 3,000. 49.The method of claim 47, wherein the Reynolds number for blood flow inthe smallest circular section of the conical internal surface variesfrom 500 to 2,000.
 50. The method of claim 47, wherein a ratio betweenthe largest circular section of the conical internal surface and thesmallest circular section of the conical internal surface is less than3.6:1.
 51. The method of claim 47, wherein the diameter of the smallestcircular section of the conical internal surface is equal to or lessthan 1.2 mm.
 52. The method of claim 35, wherein the diameter of anoutlet of the secondary channel of the infusion site is equal to or lessthan 0.8 mm.
 53. The method of claim 35, wherein a ratio between adiameter of the smallest passage section of the first fluid passage anda diameter of the first passage section is less than about 30%.
 54. Themethod of claim 35, wherein the inlet of the secondary channel of theinfusion site is tapered.
 55. The method of claim 35, wherein thesecondary channel section interposed between the inlet and the outlethas a constant circular section.
 56. The method of claim 35, wherein thecontainer of solution reestablishing blood or plasma ion balance is abag or a syringe.
 57. The method of claim 35, wherein the treatmentdevice includes a bubble trap located along the venous blood lineupstream from the infusion site.
 58. The method of claim 35, wherein thetreatment device includes an air detector operating with the venousblood line downstream from the infusion site.